Correlation between specific antibody response to wild-type BNT162b2 booster and the risk of breakthrough infection with omicron variants: Impact of household exposure in hospital healthcare workers.

BACKGROUND: The emergence of omicron variants exhibiting antigenic changes has led to an increase in breakthrough infection among individuals with a wild-type SARS-CoV-2 vaccine booster. The correlation between post-booster spike-specific antibodies and omicron infection risk remains unclear. METHODS: This prospective cohort study included SARS-CoV-2-naive healthcare workers with three-dose BNT162b2. Post-booster spike-specific IgG and interferon-γ levels were measured. Breakthrough infection was documented during a 10-month omicron-predominant period. Household and healthcare contacts were followed to identify subsequent infections. The IgG titers were additionally measured at the end of follow-up, and the titers at exposure were estimated from the two-point titers. RESULTS: Of 333 participants, 89 developed infection, of whom 37 (41.6 %) were household contacts. Kaplan-Meier curves indicated that higher IgG titers were significantly correlated with lower cumulative infection incidence (p = 0.029), whereas the interferon-γ levels were not (p = 0.926). Multivariate Cox analysis showed that increasing IgG titers were associated with a reduced hazard ratio (HR) of 0.26 (95% CI, 0.12-0.55). Household exposure posed a greater infection risk than healthcare exposure (HRs, 11.24 [6.88-18.40] vs. 2.82 [1.37-5.44]). The difference in geometric mean IgG titers of infected and uninfected participants was significant among household contacts (20,244 AU/mL vs. 13,842 AU/mL, p = 0.031). Estimation of IgG titers at exposure showed a significantly higher infection incidence in those exposed with titers of <3,000 AU/mL than in those with higher titers (79.2 % vs. 32.3 %, p < 0.001). CONCLUSIONS: Spike-specific antibodies induced by a wild-type SARS-CoV-2 vaccine booster are suggested to be effective in protecting against omicron infection. Household exposure would be a significant source of infection for hospital healthcare workers.

Successful peripheral nerve block under dexmedetomidine sedation for femoral neck fracture fixation in a 97-year-old patient.

Hip fracture is a common injury in elderly patients. In Japan, the number of super-old patients-age >90 years-with hip fractures has increased drastically over time. Available strategies for anaesthetic management for hip fracture surgery include general anaesthesia, neuraxial anaesthesia and peripheral nerve block. However, general and neuraxial anaesthesia are often avoided for various reasons, particularly in elderly patients. In recent years, peripheral nerve block has proven effective in various surgical procedures. Additionally, dexmedetomidine exhibits neuroprotective effects and has been used safely in super-old patients. Herein, we demonstrate successful anaesthetic management with peripheral nerve block under dexmedetomidine sedation for open reduction and internal fixation of a femoral neck fracture in a 97-year-old patient.

The effects of gestational transient thyrotoxicosis on the perinatal outcomes: a case-control study.

PURPOSE: To study the effects of gestational transient thyrotoxicosis (GTT) on pregnancy outcomes. METHODS: This case-control study retrospectively analyzed 7976 women with singleton pregnancies whose thyroid function was measured before 16 weeks of gestation and who delivered at ≥22 weeks of pregnancy. GTT was defined as hyperthyroidism (free thyroxine [FT4] level: ≥95th percentile) in the early pregnancy, which normalized in mid-pregnancy without thyroid-stimulating hormone receptor antibodies. Using data extracted from electronic records, we examined the association between GTT and the pregnancy outcomes (preterm delivery, gestational age at delivery, pregnancy induced hypertension (PIH), preeclampsia, placental abruption, caesarian section, birth weight, low birth weight, Apgar score, cord pH, stillbirth at gestational week ≥22, and neonatal death). We classified the cases into quartiles according to their FT4 values during the early pregnancy and investigated the association with the gestational age at delivery. RESULTS: Two hundred and eight cases of GTT and 6317 cases with normal thyroid assessments were reviewed. GTT was associated with hyperemesis gravidarum, but not with stillbirth, preterm delivery, PIH, preeclampsia, placental abruption, or low birth weight. The gestation period was shorter in patients with GTT than in those with a normal thyroid function (38.69 ± 1.79 vs. 39.07 ± 1.64 weeks, p < 0.01). Higher FT4 levels during the early pregnancy were associated with earlier delivery (p = 0.02). CONCLUSIONS: GTT was associated with a lower gestational age at delivery but not with adverse pregnancy outcomes. There was a negative correlation between the FT4 values in the early pregnancy and the gestational period.

[Effectiveness of Sacral Intervertebral Epidural Block for Umbilical Hernia Repair in Children].

BACKGROUND: Effectiveness of sacral intervertebral epidural block (S 2-3 block) for umbilical hernia repair has not been clarified. METHOD: We investigate 24 children, undergoing umbilical hernia repair; mean age of 3 years (age range: 20-65 months). Under general anesthesia, epidural block was performed at S 2-3 interspace with 1 ml x kg(-1) ropivacaine (0.2%) at injecting rate of 1 ml x sec(-1) followed by 0.25 ml x kg(-1) normal saline. RESULTS: In all cases, neither systolic blood pressure nor heart rate increased > 15% from those just before the block. Postoperative analgesics were given in 6 patients (25%) rectally. Mean time between the block and the administration of analgesic was 10.5 hours. CONCLUSIONS: S 2-3 block can be effective for postoperative pain in umbilical hernia repair.

[The use of dexmedetomidine and Airwayscope in airway management of a child with Cornelia de Lange syndrome].

We report anesthetic management of a 22-month-old child with Cornelia de Lange syndrome scheduled for palatoplasty because of cleft palate. Micrognathia and short neck of the patient suggested difficult airway management. For anesthetic induction, 1 microg x kg(-1) dexmedetomidine was loaded intravenously, followed by infusion at a rate of 0.7 microg x kg(-1) x hr(-1) with incremental inhalation of sevoflurane. During the induction, spontaneous breathing was maintained. By laryngoscopy with Machintosh blade after intravenous propofol for the purpose of laryngeal reflex inhibition, only the tip of epiglottis was seen. Then, after another intravenous propofol, laryngoscopy was performed with Airwayscope, which enabled operators to see the glottis. Then, a RAE endotracheal tube (ID 4.5 mm) was inserted. During the Airwayscope operation, pharyngeal reflex, laryngeal reflex and saliva increase were inhibited resulting in good view of the larynx and the lowest Spo2 was 94% temporarily. After intubation, anesthesia was maintained with sevoflurane, remifentanil and fentanyl. Dexmedetomidine infusion was also useful to maintain adequate spontaneous breathing and to achieve awaking before extubation.

[A case of locally advanced rectal carcinoma treated with preoperative chemoradiotherapy resulting in pathologically complete response].

An 84-year-old woman presented with the chief complaint of melena. Colonoscopy revealed a type 2 tumor that circumferentially occupied the lumen of the lower rectum about 6 cm from the anal verge. A biopsy specimen was obtained from the tumor and the patient was diagnosed with moderately differentiated adenocarcinoma. Computed tomography revealed that the rectal cancer had invaded the marginal fatty tissue, accompanied by several regional lymph node metastases with no distant metastasis. On the basis of this evidence, the tumor was staged as cT4a, cN2b, cM0 according to the TNM Classification of Malignant Tumors (7th Edition, UICC). Preoperative radiotherapy combined with an oral chemopreventive agent (RT 1.8 Gy × 25 frames; total 45 Gy, S-1 80 mg/day) was administered with trivial adverse effects. Laparoscopy-assisted low anterior resection with Japanese D3 dissection was performed successfully. The patient is doing well without recurrence after 14 months of surgery. Histological examination revealed that both the primary lesion and regional lymph nodes had no residual cancer; that is, the histological effect of the preoperative chemoradiotherapy was a pathologically complete response (pCR).

[General anesthesia for a boy with Wolf-Hirschhorn syndrome].

Wolf-Hirschhorn syndrome (WHS) is a rare chromosomal abnormality in which there is deletion of the short arm of chromosome no. 4. Features of the condition include severe psychomotor retardation, characteristic facies and various congenital midline fusion anomalies. We report the anesthetic management in a 6-year-old boy with WHS, scheduled for renal biopsy under general anesthesia. Anesthesia was induced and maintained with sevoflurane and nitrous oxide in oxygen. Mask ventilation was performed easily. After establishment of mask ventilation, laryngeal mask airway (LMA) was inserted smoothly without muscle relaxant and an adequate airway was established with a LMA. He has episodes of transient deterioration in renal function with physical stress. To decrease renal effects of perioperative stress, transversus abdominis plane (TAP) block and intravenous patient controlled analgesia (IV-PCA) were administered for postoperative analgesia. The operation ended without any complications. Anesthetic emergence was rapid and he had no pain and decline in renal function.

[Massive bleeding during and after cesarean section in a patient receiving frozen-thawed embryo transfer].

A 30-year-old pregnant woman (151 cm, 49 kg) with twin gestation who had got pregnant with frozen-thawed embryo transfer was scheduled to undergo cesarean section at 37 weeks of gestation. Combined spinal and epidural anesthesia was performed separately at the T12-L1 (epidural) and at the L3-4 interspace (spinal). The sensory anesthesia was extended to T2 and the operation was started. The cesarean delivery was uneventful and healthy 2,370 g and 2,334 g neonates were delivered. Five minutes after the delivery, placenta was removed manually from the uterus. Despite using oxytocin, methylergometrine and prostaglandin F2alpha, uterine contraction was severely impaired and massive bleeding occurred. General anesthesia was not commenced and packed red blood cells, fresh frozen plasma and cryoprecipitate were given. Uterus gradually contracted and the patient was transferred to the ward. However, massive bleeding continued postoperatively, and magnetic resonance imaging indicated retained placenta. Total hysterectomy was performed on the second postoperative day. Atonic bleeding and placental invasion should be the main causes of massive bleeding. Frozen-thawed embryo transfer might be one of the important factors for placental invasion. We have to prepare for massive bleeding during and after the cesarean section in patients receiving frozen-thawed embryo transfer.

[A case of type 4 gastric cancer with peritoneal dissemination complicating venous thromboembolism treated effectively by combination of S-1 and warfarin].

A 49-year-old female patient was admitted to our hospital for a type 4 gastric cancer with peritoneal dissemination. Two courses of paclitaxel (PTX), and eight courses of S-1 were carried out. Although a partial response was obtained, she had complications with a deep venous thromboembolism (DVT) and pulmonary embolism (PE) during the treatment. Heparin, followed by warfarin, was useful to treat the embolism. After the venous thromboembolism (VTE) disappeared, combination therapy with S-1 and warfarin were started, and the quality of life (QOL) of this patient was maintained for about one year. Fine monitoring of the international normalized ratio (INR) was required in order to prevent side effects of blood coagulation by S-1 and warfarin coadministration. This case suggests that the combination therapy of S-1 and warfarin may be a safe and effective treatment able to prolong time to progression against a type 4 gastric cancer with VTE.

Usefulness of FDG-microPET for early evaluation of therapeutic effects on VX2 rabbit carcinoma.

PURPOSE: The aim of this study was to determine the potential use of high-resolution FDG-microPET for predicting the primary effects of radiotherapy and/or hyperthermia on tumor-bearing rabbits. METHODS: Twenty-eight VX2 xenografts in the thighs of rabbits were divided into the following 5 treatment groups: radiotherapy at a single dose of 10, 20 or 30 Gy, hyperthermia (43 degrees Celsius, 1 hour), and the combination of radiotherapy and hyperthermia (10 Gy + 43 degrees Celsius, 1 hour). FDG-microPET images were obtained by using a microPET P4 system at pretreatment and at 24 hours and 7 days after treatment. For the evaluation by FDG-microPET, tumor/muscle (T/M) ratios, retention index [RI = (T/M ratio at 120 min - T/M ratio at 60 min) / T/M ratio at 60 min], and time activity curve (TAC) were acquired. RESULTS: We divided the xenografts into a responder group (partial response + stable disease, n=14) and a non-responder group (progressive disease, n = 14). The T/M ratio at 24 hours after the treatment in the responder group was decreased remarkably with that at pre-treatment (p < 0.05), while in the non-responder group it showed no significant change between the time points. The RI and TAC patterns were comparable to T/M ratios in each treatment group. T/M ratios, RI, and TAC indicated marked changes at the time point of 24 hours in the responder group, although the tumors did not show any significant hange in volume at that time. Photomicrographs of sections showed that the number of viable tumor cells in the responder group decreased at 24 hours after treatment and that inflammatory cell infiltration was marked and almost all viable tumor cells had disappeared by day 7 after treatment. CONCLUSION: These results suggest that early evaluation by FDG-microPET, especially 24 hours after treatment, is useful to predict the primary effects of the treatment. Histological analysis showed that inflammatory cell infiltration at 7 days after treatment was considered to be a cause of accumulation of FDG in the tumors that showed a significant decrease in tumor cell number. This false-positive should be noted when predicting tumor response by FDG accumulation.

Accelerated hyperfractionated irradiation with concomitant boost for stage II laryngeal cancer and locally advanced head and neck cancer.

OBJECTIVE: This study was conducted to evaluate the efficacy and feasibility of our accelerated hyperfractionation with concomitant boost for stage II laryngeal cancer and stages III-IVb locally advanced head and neck cancer. PATIENTS AND METHODS: From January 2000 to October 2001, eight patients with AJCC 1998 stage II laryngeal cancer and 11 patients with AJCC 1998 stages III-IVb locally advanced head and neck cancer underwent accelerated hyperfractionated radiation therapy. For the stage II laryngeal cancer, radiation was delivered at a 2.0 Gy fraction a day, 5 fractions per week for the first 3 weeks, then 2 fractions (1.8 and 1.2 Gy) a day, 5 times a week for 2.5 weeks, with total dose of 69 Gy. For stages III-IVb head and neck cancer, radiation was given at a 1.8 Gy fraction a day, 5 fractions per week for 6 weeks and a boost was added up to 70.5 Gy with 1.5 Gy as a second daily fraction during the last 2.2 weeks. Among the patients, 16 (84%) received concomitant chemotherapy, mainly with low-dose carboplatin. Acute toxicity based on RTOG criteria and tumor response at 1 month post-treatment were estimated as initial effects. RESULTS: The overall response rate was 100% in patients with stage II laryngeal cancer and 91% in patients with stages III and IVb head and neck cancer. The incidence of grade 3 or worse acute effects was 47%. Eighteen patients (95%) completed radiation therapy without interruption related to acute side effects, while one had prolongation of the treatment for more than 1 week because of neutropenia. CONCLUSIONS: Our results demonstrated that accelerated hyperfractionation, mostly combined with concomitant chemotherapy, had a good overall response rate with acceptable toxicity in stage II laryngeal cancers and stages III-IVb head and neck tumors.

Use of FDG-microPET for detection of small nodules in a rabbit model of pulmonary metastatic cancer.

OBJECTIVE: The performance of microPET using 18F-FDG was evaluated in a rabbit model of hematogenous pulmonary metastatic cancer. METHODS: A total of 15 Japanese white rabbits and VX-2 carcinoma were used in this study. In the microPET study, tumor-bearing rabbits were administered intravenously 74 MBq of 18F-FDG, and 30 min later, the emission data were acquired for 60 min. The transmission scans were performed with a 68Ge/68Ga external point source. To augment the anatomical information, we performed multi-detector row computed tomography (MDCT) in the combination with MDCT and microPET on 10 rabbits. The other 5 rabbits were followed once a week for 5 weeks only by microPET. Tumor/muscle (T/M) ratios were used for quantitative evaluation in this study. RESULTS: Multiple pulmonary nodules were detected by MDCT and microPET starting 14 days after the tumor injection. The high-uptake lesions in the lung detected by microPET corresponded well to the tumors detected by MDCT. The smallest nodule detected by microPET was ca. 1.5 mm in diameter. Overall, 87 nodules were detected by MDCT and the ratios of lesions detected by microPET to those by MDCT were 35.3%, 77.5%, and 90% for tumors equal to or smaller than 2 mm, 2-4 mm, and 4-6 mm in diameter, respectively. The respective T/M ratios were 2.41 +/- 0.41, 2.93 +/- 0.55, and 3.34 +/- 0.71. The T/M ratio increased with tumor size, but it was similar in each tumor size category. In the 35-day follow-up protocol, it was possible to follow sequentially the same tumor by the microPET. CONCLUSIONS: By FDG-microPET, it is possible to evaluate tumors larger than 2 mm in diameter and to follow the growth of individual tumors. Our results also suggest that the rabbit model of VX-2 pulmonary metastasis is a stable experimental model for evaluation using FDG. Monitoring of the therapeutic effects of anticancer drugs and radiation therapy could be tried by using this model and microPET.